Thanks for presentation, and I appreciate Renée and Kelvin. Renée Galá, President, Chief Operating Officer, and Kelvin Tan, Chief Medical Officer. Thank you for joining. I also thank Jack Spinks, who I met earlier, for a lot of the help with getting organized and questioning and so forth. So, just to kick us off, Renée and I were just talking just on a brief overview of the program and where you stand right now, maybe, and then ultimately roll into pipeline and so forth. And just basically, so you've raised guidance past couple quarters, obviously. So I thought it'd be helpful just to start out and talk about each of the kind of three growth drivers, and then we can kind of go into pipeline and evolve from there, if that's okay.
Yeah, sure. That sounds great. Well, first of all, thank you for having us, Larry. We appreciate the invitation, and thank you all for joining us. Maybe just before we get started, though, I'll remind you, we will be making forward-looking statements today, so please see our website and SEC filings for more information about our business, including risk factors. Should we refer to financial guidance? We're not updating or reiterating today. This is all as of our third quarter earnings call on November 8th. And also, should we make reference to non-GAAP financial measures, you can find full reconciliations on our website. So just a very quick overview for those of you a little less familiar with Jazz. Jazz is a fully integrated global biopharmaceutical company. We have a suite of diverse marketed medicines as well as a robust pipeline of product candidates.
We focus primarily in neuroscience and oncology. Within neuroscience, we're a leader in sleep with XYWAV, which is approved for the symptoms of narcolepsy, and it's the first and only drug approved for idiopathic hypersomnia, another rare sleep disorder. Also within neuroscience, we have Epidiolex, which is the first and only cannabinoid-based medicine. It's approved for certain rare forms of epilepsy. Then we have a rapidly growing oncology portfolio. Four approved medicines. We expect to generate approximately $1 billion of revenue this year, at the midpoint of our financial guidance. This commercial portfolio has rapidly transformed over the last few years. In 2020, we had approximately $2.4 billion of revenue, 75% of which was coming from a single sleep product.
If you fast-forward to today, 2023, we are aiming to achieve approximately $3.8 billion in total revenue across the year. Importantly, the composition of that revenue looks very different. We have a diversified set of products now. No one product is dominating our income statement, and this is a durable product portfolio across sleep, epilepsies, and oncology. As we think about what the strength of that business has done for us, it's enabled us to be in a strong financial position. We generated over $900 million in cash flow in the first nine months of this year. We ended the third quarter with $1.6 billion of cash, and importantly, that gives us the flexibility to keep investing in the growth drivers you'd mentioned, Larry, which we'll go into in a few minutes.
We have the ability to invest in our commercial growth drivers, invest in our pipeline, and also in corporate development, which has been an important pillar for us in achieving revenue growth, achieving revenue diversification, and also continuing to expand our pipeline. Importantly, we've also in the Q3, Q2 and Q3 timeframes, been buying some of our stock back just based on the belief that there's a quite a bit of unrealized value currently in our stock. We purchased about $175 million of our stock, and that has not limited our ability to be able to continue to invest. It hasn't compromised our ability because we're so well capitalized. Moving on to the pipeline, we've also transformed that part of our business. We're now fully, fully capable end-to-end capabilities in research and development.
We have a broad early development pipeline. We have a research group now internally that's advancing early work as well as in our late-stage pipeline. 2024 is a very exciting year for us, and we expect to have up to five late-stage readouts, between now and the end of 2024. I think of 2024 as being a bit of the year of the pipeline for us. So it's an exciting time for us in general. We think we're very well positioned to achieve Vision 2025, which of course, has revenue goals, a pipeline goal, and operating margin objectives. And with, you know, with that, I'm happy to turn to Q&A. If you'd like for us to start on some of the growth drivers, we can certainly do that.
Yeah, that'd be great. And thank you for that introduction. I'd love it if we could start by framing the oxybate franchise right now. There's obviously been some-
All right.
Oh, sorry. Oxybate franchise and, you know, framing as kinda the $2 billion franchise is kind of the goal, I believe is a part of the Vision 2025. There's obviously been some competitive little change in the competitive landscape. Can you just speak to your vision on the, that franchise broadly and the transition and where you stand relative to what your expectations have been and so forth?
Yeah, absolutely. So we do have an objective of in 2025, our oxybate sleep franchise generating approximately $2 billion in revenue. XYWAV itself is currently the oxybate of choice, and there's a broad recognition within the HCP community of the benefits of low sodium, in particular for diseases like narcolepsy, idiopathic hypersomnia, which tend to carry increased cardiovascular risk. And these are chronic diseases, so patients generally take their medication each and every day. And the sodium load that comes along with all of the other oxybates available on the market, which are high sodium oxybates, is remarkably higher and carries additional risks for these patients. So we are confident that XYWAV will remain the oxybate of choice for the foreseeable future. Within narcolepsy, we've continued to see strong adoption with XYWAV.
With idiopathic hypersomnia, as I'd mentioned, XYWAV is the only medicine approved. It's the only oxybate, but the only medicine approved for idiopathic hypersomnia, and it's approved for the entire condition. So we do see that as an important growth opportunity-
Yeah.
-for us. And XYWAV has continued to perform quite well, even in the face of-
Yeah
... competition from authorized Generics this year, as well as branded competition.
Branded. Okay. Do you in terms of investing in, in that franchise, where, where are you today in, in terms of just investing in that franchise to drive it to $2 billion?
Yeah. So-
Uh.
Absolutely. So XYWAV is annualizing today-
Yeah
... at $1.3 billion. The entire franchise is already annualizing at about $1.9 billion. What comprises our $2 billion objective for 2025 are the sales of branded XYWAV, sales of branded XYREM, and then royalties that come from the sales of authorized generics of XYREM. So, we do think we're on track for that goal. And keep in mind, with respect to our authorized generic royalties, there's three different royalty structures in place with respect to Hikma, which is the only unlimited authorized generic. We are currently in the second half of 2023, in a structure whereby we and Hikma each receive meaningful revenue, meaningful economics from the sales of their authorized generic.
And then beginning in 2024, the royalty rate to Jazz on the sales of that product increased to a high double-digit percentage fixed royalty, and they stay there through the remainder of the authorized generic period.
Okay.
That's important because at that point in time, the value of a patient on an authorized generic Hikma product.
Right
to Jazz is not meaningfully different than the value of a patient on high sodium XYREM.
Okay.
Now, keep in mind that we think any patient that is on a high sodium oxybate is, you know, a good candidate for going on low sodium XYWAV, and that's why we-
Right
... continue to have confidence in that franchise.
Mm-hmm.
In terms of specific investments, we are investing behind narcolepsy. We think there's continued growth there. It's very likely that the overall market expands-
Yeah
... because you have another branded competitor out visiting with HCPs. That generally has the impact on markets of, the overall market expanding. But most importantly, with being the only medicine approved for IH, we think that is a really important growth driver for XYWAV. We did announce in the most recent quarter that we were expanding our investment, in particular for IH. With that, we've actually, we're investing in a separate small sales force that will be only targeting idiopathic hypersomnia.
Awesome.
Some of those sleep specialists that have a lot of IH patients that are currently less familiar with oxybate, so we're excited about that. And then we're also continuing to invest in evidence generation as well as additional data to educate HCPs on the benefits of low sodium. And maybe, Kelvin, you'd like to comment on that.
Yeah.
Sure. So, specifically with regards to investing in data generation for oxybate and specifically XYWAV, there are two areas that we are focused on. Both of these trials are actually on clinicaltrials.gov. One is looking at blood pressure.
Mm-hmm.
So looking to demonstrate that when you transition a patient from XYREM or a high sodium oxybate to a low sodium XYWAV, you get benefits of blood pressure changes. But also looking at the flexibility and the utilization of individualized dosing in particular for XYWAV. Now, we continue to hear from physicians, from patients, the importance of individualized dosing... and that is a key differentiator for us for XYWAV, which is low sodium, is that because it is dosed twice nightly, because within our label, you can dose in an asymmetric fashion in terms of the whether you give a higher or a lower first and second dose.
That individualized dosing is becoming increasingly noticed as an important differentiator and important for patients in terms of how they want to live their lives, whether they want to adjust their dosing because perhaps they need to get up early in the morning. And that's something that you don't get with a fixed-dose oxybate, where once you've given that dose, that's it. If you were to wake up, for example, earlier in the day in the morning, you're unable to take a second dose. So those are the two areas that we're investing in specifically, is around the blood pressure benefits of a low sodium-
Great.
XYWAV, as well as the individualized dosing.
Okay, great. Thank you for that. Can we transition over to Epidiolex? And again, that's, I believe you're in the Vision 2025. That's a roughly, I think, billion-dollar goal ultimately. Can you speak to that as a target reference point and investing in that product and where we are, we stand today, you know, as far as meeting those patterns?
Yeah, absolutely. So Vision 2025, from a revenue perspective, envisions $5 billion of revenue in 2025.
Yeah.
We envision that coming from three different places. About $2 billion coming from the oxybate-
Yeah
- franchise, another $2.5 billion coming from oncology and Epidiolex-
Yeah
- combined, with each of those franchises generating north of $1 billion.
Okay.
And then another $500 million coming from corporate development. You know, again, we've been very active in that area over the years. So with respect to Epidiolex specifically, I can talk about some of what we're seeing in the commercial franchise and where we're going.
Okay, great.
And then I'd invite Kelvin to describe a bit about EPICOM, a recent study that we're leaning into. So, Epidiolex is a global product for us, so we are seeing nice growth in the U.S. We're also continuing to execute launches throughout Europe. We're approved and reimbursed in the five major markets and continue to see additional countries come on, and then within countries, additional indications come on. So good opportunity for expansion there, and we're also executing a pivotal study that we expect to read out in the second half of next year to support an eventual filing in Japan, which we think will also be another important market for us. In terms of where the growth is coming from, we're seeing growth from a number of different areas. One of the more important areas is related to data generation.
So we have a lot of data that has come from different databases that we have currently showing a synergistic effect of the use with clobazam, the use of Epidiolex with clobazam.
Yeah.
Many epilepsy patients are already on clobazam, and so the effect on seizure reduction has been much more meaningful than physicians are used to seeing-
Right
- with respect to the data that we've shared, so that's driving increased use. We're also through what's called the EPICOM data. It's a caregiver survey we executed. Being able to see benefits beyond the seizures in behavioral improvements, also cognition improvements, which is really important to caregivers for-
Right
Parents, in particular, of children with these rare, severe forms of epilepsy. So that's really creating a lot of momentum. We've also seen uptake in the adult and long-term care environment, as well as additional dosing.
Mm-hmm.
With respect to increased dosing, we're often seeing better efficacy, better results when people actually titrate up to the right dose.
Mm-hmm.
Those are all drivers of what?
Yeah
... is creating the growth with Epidiolex and giving us continued confidence that we're on track for the medicine-
Yeah
- generating over $1 billion in revenue.
Yeah.
Kelvin?
Yeah, I'll just add, really, so, as Renée was saying, it's well recognized, the benefits that Epidiolex offers in terms of seizure control. But actually, what's really taken us and really inspired our, you know, future evidence generation work is the feedback that we're hearing from caregivers and from physicians, that Epidiolex not only is giving seizure control, but beyond seizure control, is improving higher executive function. And you have to remember, these are typically children and some older patients as well, who, you know, have significant syndromic disorders, which impairs their higher executive function. And so based upon that information, we actually launched this year a new study, EPICOM or Epidiolex Comorbidities, which is specifically looking at patients with tuberous sclerosis.
We're dosing patients prospectively and monitoring them in terms of their executive function, specifically looking at their most worrisome or most bothersome symptoms when it comes to speech, behavior, neuropsychiatric disorders as well. That's a study we're very excited to launch and I think speaks to our confidence around the benefits that you get with Epidiolex beyond just seizure control.
Okay, great. Thank you. I'm watching the clock here. One thing I wanna make sure we get to. I wanna ask Mark, kind of Rylaze, you know, the growth product, but I'd prefer just to transition over the conversation about the pipeline. Kind of starting with, with Zani in particular. It seems, appears very promising. I believe you've laid out kind of a you know, potential peak revenue target of $2 billion, which obviously is very opportunistic. Can you just talk about the submission and, and, and the 2024 readout and kind of for us, maybe just a little bit of history and just take us kind of up to speed, not just with Zani or other pipeline products, but particularly focusing on Zani, if you could.
Yeah, sure. Well, maybe I'll start, and then Kelvin, you can dig in there. We are incredibly excited about zanidatamab. This is another example of an excellent corporate development transaction that we were able to execute $50 million upfront to be able to have the option once seeing what was the initial meaningful data set in biliary tract cancer, then an opt-in. And so we closed that transaction in 2022, and I've only continued to be excited about the data that's come forward. We do believe it has the potential to be a $2+ billion revenue product for us. It's the most de-risked program in our pipeline and-
Mm-hmm.
—and one that we're investing heavily in. And in fact, when we raised our R&D guidance from $700 million-$800 million for the full year of 2023-
That's much.
primarily driven exactly by accelerating and expanding that development program.
Yeah. Thank you, Renée. So it absolutely, we do view it as our most de-risked program, and, you know, we disclosed it just a few weeks ago that we'll be initiating a rolling BLA submission for zanidatamab, seeking an accelerated approval in second-line biliary tract cancer. And we expect to complete that submission by the first half of 2024. We do, as you were describing, have an ongoing trial, a frontline pivotal trial in gastroesophageal adenocarcinoma, a much bigger opportunity, as much as 63,000 patients within our territories. And that study is progressing well, and we expect the data to read out for that in 2024. But as Renée was saying, our confidence around zanidatamab has continued to increase as we see more and more data being released through this year.
Earlier this year at ASCO, some really compelling data in biliary tract cancer, where the confirmed objective response rate was 41.3%. Those data were invited to be best of ASCO in terms of the reception that we got from the community. And then subsequently, at ASCO GI, we presented data looking at the combination of zanidatamab and chemotherapy, also in gastroesophageal adenocarcinoma, which demonstrated, at that time, an unprecedented level of confirmed objective response rate of 59%.
Mm-hmm.
And then only recently at ESMO, this year, BeiGene presented data looking at the triplet, which is zanidatamab, chemotherapy, and tislelizumab, in terms of treating gastroesophageal adenocarcinoma. And again, that showed a confirmed objective response rate of about 76%. So all of these data, which we've been rolling out through this year, has continued to build our confidence around the opportunity that we see for zanidatamab, and hence, the increased investment within R&D.
Okay. As we look into 2024, what are like the potential catalysts, if you will? That obviously you have the readout, but even beyond that, like, what are you looking for as kind of hurdles on Zani going forward?
Yeah, so within the period of 2024, as you said, the most important data that would be coming out will be in GEA.
Okay.
We do have other studies which are ongoing. We haven't disclosed precisely the dates of which those data will be reading out, but we do have programs in breast cancer as well. We were invited to a very highly prestigious platform, which is the I-SPY platform, where we're looking at zanidatamab in breast cancer as a neoadjuvant treatment. Again, speaking to the highly differentiated nature of zanidatamab, it gives the opportunity for patients with breast cancer, particularly those with an early diagnosis, not to require a high chemo payload, which we know can be very, you know, cause significant side-effect profile for patients. We do have breast cancer programs ongoing. We also have opportunities in breast cancer, not just early, but later stages, and also at different lines of therapy.
So all of this is continuing to give us confidence around data flow. Whilst we haven't specifically disclosed exactly when some of these will be coming through, you should be reassured that there will be data flow in the coming years.
Okay, great. Can just evolving from there, Kelvin, can, and maybe Renée, touch on some of the other, you know, readouts expected for, you know, that are forthcoming kind of next, you know, 2024, and a coup- you know, other opportunities in the pipeline, I, I guess I would-
Of course.
-reference.
So as Renee said, you know, she's calling it the year of the R&D pipeline, and I couldn't agree more. So in January of 2024, we're expecting to see readout from JZP150, which is our treatment for post-traumatic stress disorder. Later in the year, in the first half of 2024, JZP385, which is a treatment for essential tremor, we expect to see top-line data there. And Renée has already spoken to what we're expecting from Epidiolex with our pivotal study in Japan, which we expect in the second half of 2024. Turning to oncology, we also have a trial in which we are partnering with Roche Genentech, where we're looking at lurbinectedin or Zepzelca in combination with Tecentriq in frontline extensive-stage small cell lung cancer.
I've already spoken to opportunities also for zanidatamab. But I think really coming back to Renée's earlier point, what you will also see is that we do have a combination of end-to-end capabilities within R&D, so we're expecting data also within our early stages as well as our late-stage programs. We do believe those late-stage programs could be very important catalysts for Jazz.
... and maybe just to build on that further. So all of these late-stage readouts-
Yeah.
that Kelvin is describing are in areas where there's a significant unmet medical need.
Mm.
So when you look at PTSD and essential tremor, for example.
Yeah.
you have decades that have gone by without real innovations for-
Yeah
-patients here. So we're really excited about the opportunities-
Mm.
to not only, like, look at important markets, but really help patients.
Yep, great. Great. I know we had talked about a little bit earlier, and there was some headline, actually, in JZP441, and we just said phase one. Can you just maybe make a quick, brief, you know, discussion point on that, if you will? Just that, you know, it was phase one and is very, very early stage-
Yeah.
and not, you know.
Sure. So yesterday we did announce-
Relevant, yes.
That for JZP441, which is our orexin-2 receptor agonist, we did achieve proof of concept in healthy volunteers looking at MWT or maintenance of wakefulness testing. We did also announce yesterday our decision to pause our program as we had identified some emerging information around visual disturbances and cardiovascular effects. Do you want to make clear? This is a phase one program-
Yeah.
As you were saying, Larry. So it is early days, and if you look across the board, I think it's fair to say that everyone is at an early stage. And, you know, while there is a lot of excitement around the orexins, this is a complex program. What I would share, though, I think, is that what we're seeing from the data that's emerging is, yes, evidence that it's encouraging, that we're seeing proof of concept with orexin-2 receptor agonists. But actually, it's important to get the balance with the therapeutic index right, whether that's safety and tolerability. We're hearing already some reports of if you don't quite get your half-life right, you might get extension into the evening and get issues with insomnia.
Mm-hmm.
So that's something that we know that the you know the community is working through right now, is how do you get-- how do you answer some of those questions around PK/PD, half-life, et cetera, to ensure that you're getting that right balance? And what I think I'll just finish and say, what I would, we would, you know, generally conclude from the evidence we're seeing so far is that orexin-2 receptor agonists are likely to be daytime wakeful... Used as daytime agents in terms of promoting-
Okay
wakefulness, and actually, therefore, used complementary to a backbone of an oxybate therapy. So we see them as, you know, something that would complementary will work together.
Yeah, yeah. Okay, great. Thank you. We only have a couple few minutes here, so I wanna see if there's any questions in the audience wanted to address quickly.
Thanks. I apologize if you just live with this. Sure, your $2 million constant, that assumption, does that mean Defitelio or Lumryz's market share, both for the IH and for the insomnia things?
Yeah, thank you. So you're asking for specific assumptions relative to the competitive environment for the $2 billion in revenue that's assumed in 2025 for our oxybate franchise. So certainly, we've made assumptions around Lumryz's uptake, as well as, you know, what sort of market share you might see from the authorized generics. We have not provided a specific breakout of XYWAV in narcolepsy versus IH or the breakout specific to our authorized generic royalties or branded XYREM. But what I will say is, we expect the vast majority of that $2 billion revenue target to come from XYWAV, the combination of narcolepsy and IH. We do see IH as an important growth driver for us. Again, XYWAV is the only medicine approved.
For this condition, we currently have approximately 2,550 patients on therapy coming out of the third quarter for IH, and there are approximately 37,000 patients in the system that are diagnosed and actively seeking treatment for idiopathic hypersomnia. So we do see that as an important growth driver. With respect to Lumryz's uptake, we do expect that some patients are going to want to try a fixed-dose, high-sodium competitor, and we have seen some uptake there. But broadly speaking, what we've seen across 2023 to date has been exactly in line with or even better than our overall expectations. In the second quarter, we increased our overall revenue guidance, and the neuroscience guidance, primarily driven by the strength of our oxybate franchise.
Then in the third quarter, we reiterated our neuroscience guidance, and then once again, raised our total revenue guidance, this time, underpinned by our oncology franchise. While we don't have specifics to share on our assumptions, I would just say we do assume there'll be some market uptake, and, and that is all going according to our expectations.
Great. I think we're about at the end, but I feel like I have to ask this question, the strategic options question. I don't know what you're sharing, you know, what you could share with the audience, but if there's any thoughts on maybe timing or where this could, you know, or just where your head is at as it relates to strategic options and kind of that messaging.
Yeah. So to clarify, I think you're asking about the Bloomberg article-
Yeah.
That was published, which, to be clear, was not informed by any comments that we, Jazz, have made. And we, you know, of course, you won't be surprised to hear me say-
Yeah
... we don't comment on market speculation or rumors, but our focus is on continuing to grow and diversify our business.
Okay.
Our focus is on executing Vision 2025, growing our top line, investing in the pipeline to continue to create a durable, sustainable business. And we're in an incredible position to be able to-
Yeah
continue to invest in that business, given our financial strength. We've deleveraged our balance sheet coming out of the GW acquisition-
Yep.
delevered ahead of schedule, as many know, and feel that we're very well positioned to be able to execute on our current strategy.
Yeah. And to that end, you clearly delevered ahead of what was laid out at the transaction with GW. Is there today, I know you've talked about potentially acquisitions could come into the fold at some point. Is there a leverage profile in your mindset? You know, obviously, we're kind of low fives, I guess, at the time of the GW deal and ever materially lower tight, huge cash balances. Is there a leverage profile that is a peak leverage for you, it's, if you will? Is the GW level kind of a peak leverage metric for you in the way of if you did an acquisition? You know, the next acquisition? Is that the way to think about it? Is that a fair assessment?
Yes, it's relatively fair.
Yeah.
But, I think it needs a bit of context in the sense that at the time we did the GW transaction, we were comfortable going up to that leverage ratio because we felt what was right for the business was to do a transformational transaction at that time.
Yeah.
We acquired a growing product, we acquired a pipeline, we acquired incredible capabilities coming from our GW colleagues, and that met our needs at the time.
Yeah.
We were thrilled with the transaction. We were also comfortable leveraging up because we felt confident that we could delever quickly based on the EBITDA that GW was bringing. So when we think about leverage ratios, it's also, you know, how quickly do we expect-
Right.
You know, we can pull different levers in our business.
Yeah.
We're not in a place right now where we feel we need to do a transformative transaction.
Right.
We do think that we could do a transaction for several billion dollars and stay within, you know, our credit ratings-
Yeah
... do that comfortably with respect to the strength of our balance sheet. We are prioritizing commercial assets-
Yeah
where we can continue to leverage that global footprint.
Mm-hmm.
But we're also active in the pipeline space.
Okay, great. Well, thank you. Thank you, Renée. Thank you, Kelvin. Thanks to the team as well for your-